缺血后处理联合预处理对大鼠脑组织HSP70的表达和脑缺血再灌注损伤的影响

Effect of Ischemic Pre-Postconditioning on the Expression of Heat Shock Protein 70 and the Injury of Global Cerebral Ischemia-Reperfusion in Rats

目的:探讨缺血后处理、缺血预处理及两者联合应用对急性全脑缺血再灌注损伤大鼠脑组织超微结构及热休克蛋白70(HSP70)的影响及其可能的机制。方法:采用改良的四血管法制造大鼠全脑缺血模型,实验分5组,假手术A组、缺血再灌注B组、缺血预处理C组、缺血后处理D组,联合处理E组,各组动物分别于再灌注结束后(6,8,24h)断头处死。采用免疫组织化学染色的方法测定大鼠脑组织中HSP70灰度值;电镜观察脑组织超微结构的变化。结果:缺血再灌注损伤后,各组脑组织HSP70表达增强,在各时间点E组HSP70表达明显高于B组、C组、D组,差异有显著性(P<0.01),C组与D组在各时间点无明显差异(P>0.05);电镜下观察B组脑组织损伤最重。E组脑组织损伤最轻,C组和D组优于B组。结论:短暂脑缺血再灌注损伤可诱导HSP70表达,有利于脑缺血再灌注后损伤神经元的修复。

Objective： To observe the effect of postconditioning, preconditioning and pre- and post-conditioning on the expression of heat shock protein 70 （HSP70） and ultrastructure of brain and injury of global cerebral ischemia reperfusion in rats, and to explore the mechanisms. Methods： The SD rats were randomly divided into five groups： group A （sham operation group）, group B （global cerebral ischemia reperfusion group）, group C （preconditioning group）, group D （postconditioning group）, and group E （pre- and post-conditioning group）. The model of global ischemia and reperfusion was established in group B, C, D, and E by improved Pulsinelli＇s method. The rats were sacrificed at 6, 8, or 24 hours after ischemia-reperfusion. The expression of HSP70 in brain tissue was examined by immunohistochemistry, and the uhrastructure of cortex was observed by electron microscope. Results： The expression of HSP70 in brain tissue of rats after cerebral ischemia-reperfusion injury increased reactively at the 6th hour, reached the peak at the 8th hour, and decreased at the 24th hour in group E, which was significant different from that in group B, C, and D, respectively. In group B, the uhrastructure image presented fragmental destruction of neuronal membrane, swelling mitochondria, aggregation of chromatin, or neuron apoptosis, while in other groups, especially in group E, the above ultrastructural damages were ameliorated markedly. Conclusion： The expression of HSP70 is induced in the brain of rats after cerebral ischemia-reperfusion, and through which, pre- and post-conditioning contributes to the protection of brain neurotrophic cells after ischemia-reperfusion.